Compositions useful in treatment of ornithine transcarbamylase (OTC) deficiency
AssigneeThe Trustees of the University of Pennsylvania
InventorsLili Wang, James M. Wilson
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Abstract
Viral vectors comprising engineered hOTC DNA and RNA sequences are provided which when delivered to a subject in need thereof are useful for treating hyperammonemia, ornithine transcarbamylase deficiency and symptoms associated therewith. Also provided are methods of using hOTC for treatment of liver fibrosis and/or cirrhosis in OTCD patients by administering hOTC.
Claims18
A recombinant adeno-associated virus (AAV) having an AAV8 capsid and packaged therein an expression cassette comprising:
- a) a 5′ AAV inverted terminal repeat (ITR) sequence;
- b) an ornithine transcarbamylase (OTC) coding sequence;
- and
- c) a 3′ AAV ITR sequence,
- wherein the OTC coding sequence is operably linked to a liver-specific promoter sequence,
- and wherein the OTC coding sequence comprises a sequence at least 96% identical to SEQ ID NO:
- 5 that encodes a human OTC protein of SEQ ID NO:
- 1.
A recombinant AAV having an AAV8 capsid and packaged therein an expression cassette comprising:
- a) a 5′ AAV inverted terminal repeat (ITR) sequence;
- b) an ornithine transcarbamylase (OTC) coding sequence;
- and
- c) a 3′ AAV ITR sequence,
- wherein the OTC coding sequence is operably linked to a liver-specific promoter sequence,
- and wherein the OTC coding sequence comprises SEQ ID NO:
- 5.
An scAAV having an AAV8 capsid and packaged therein an expression cassette comprising:
- a) a 5′ AAV ITR sequence;
- b) a liver-specific promoter sequence;
- c) an ornithine transcarbamylase (OTC) coding sequence comprising SEQ ID NO:
- 5 or a sequence at least 96% identical thereto that encodes a human OTC protein of SEQ ID NO:
- 1, wherein the engineered nucleic acid sequence is operably linked to the liver-specific promoter sequence;
- d) a poly A sequence;
- and
- e) a 3′ AAV ITR sequence.
An scAAV having an AAV8 capsid and packaged therein an expression cassette comprising:
- a) a 5′ AAV ITR sequence;
- b) a liver-specific promoter sequence;
- c) an ornithine transcarbamylase (OTC) coding sequence comprising SEQ ID NO:
- 5;
- d) a poly A sequence;
- and
- e) a 3′ AAV ITR sequence.
An scAAV having an AAV8 capsid and packaged therein an expression cassette comprising:
- a) a 5′ AAV ITR sequence comprising a 5′ AAV ITR sequence in which a D-sequence and a terminal resolution site are deleted;
- b) a TBG promoter sequence;
- c) an ornithine transcarbamylase (OTC) coding sequence comprising SEQ ID NO:
- 5 operably linked to the TBG promoter sequence;
- d) a poly A sequence;
- and
- e) a 3′ AAV ITR sequence.
Dependencies are inferred from the claim text.